Visualising the fine structure of heart muscle in 3D using electron tomography

Unravelling the fine structure of the myocardium by modern electron microscopy: structural basis of regulation and disease

Hypertrophic cardiomyopathy (HCM) is a heart condition that runs in families and affects the heart’s muscle. In HCM the heart’s muscle becomes thickened and stiff, making it harder for the heart to pump blood around the body. It is a relatively common condition that can cause shortness of breath and palpitations. It is the most common cause of sudden cardiac death in young people. Recently researchers have found that tiny changes to a gene coding for a protein called myosin binding protein C (MyBP-C) is a major cause of HCM and research is underway to find out why this protein is so important. Dr Pradeep Luther at Imperial College London is using state-of-the-art technologies to look in detail at the proteins that make up muscle fibres in the heart. In this programme Dr Luther will use a sophisticated technique called electron tomography to understand the fine structure of MyBP-C and how changes to it affect the structure of the muscle tissue, and therefore how it contracts. The exact arrangement of different muscle components in three dimensions is crucial for proper muscle contraction. To study the 3-D arrangement of the muscle fibres, Doctor Luther will use a high-powered electron microscope to visualise muscle tissue in such detail that individual molecules can be seen. Rotating the muscle slowly then allows the researchers to build a 3-D picture of the structure. The technology will allow Dr Luther and his team to work out how important proteins like MyBP-C interact with other muscle proteins and how changes to the proteins affect their structure and function, leading to disease. For the first time, MyBP-C will be seen in intact heart muscle in 3-D. This will help the team understand what goes wrong in HCM, and help identify new ways to treat it.